Sexually transmitted infections (STIs) are a leading cause of morbidity and mortality in young women. Little is known about the effects of reproductive hormones on susceptibility to STIs. The overall goal of this project is to develop in vitro organotypic models of human vaginal and cervical tissues for studies of endocrine effects on female genital tract immune defense and STI infection mechanisms. Three dimensional, highly differentiated vaginal-ectocervical full-thickness (VEC-FT) and endocervical tissue models will be reconstructed under the influence of female reproductive hormones to reproduce tissues representative of the various phases of the reproductive cycle. The reconstructed tissue models will be validated by comparing gene expression patterns with those of native human vaginal and endocervical tissue harvested at defined stages of the menstrual cycle. Endocrine effects on innate immunity and susceptibility of the VEC and endocervical tissue models to STI-causing microbial infections will be examined. Once infection/transmission in the organotypic tissue models is established, the effect of infection on tissue characteristics and the expression of innate immunity factors, chemokines, and cytokines will be determined. Finally, safety and efficacy testing of anti-microbial agents will be performed.